Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to neurotransmitters, hormones, acting through the blood stream, also play a role in behavior. To test the potential contribution of genetic variations in hormone receptors we have examined the association between the alleles of the dinucleotide repeat of the estrogen receptor 1 gene (ESR1) and the nine subscores and total score of the SCL-90 in a group of 179 adult males treated for substance abuse. Based on our prior hypothesis that the length of repeat polymorphisms may play a direct role in gene regulation, the alleles were divided into two groups, short (S) and long (L). ANOVA of the SS, LS, and LL genotypes showed a significant association at alpha </=0.05 for three of the SCL-90 scores: anxiety, phobic anxiety, and total symptoms. Of these the anxiety score remained significant at a Bonferroni corrected alpha of </=0.005. By regression analysis, the ESR1 gene accounted for 7% of the variance of the anxiety score (P </= 0.0004). These results are consistent with a role of the ESR1gene in human behavior. Since estrogen levels are much higher in women than men, this could account for the increased frequency of anxiety in women.
Mol Psychiatry 1999 Jul
PMID:Potential role of the estrogen receptor gene (ESR1) in anxiety. 1048 55

Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol O-methyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT x 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR x D4DR (F = 6.18, P = 0.03) and COMT x 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry (2000) 5, 96-100.
Mol Psychiatry 2000 Jan
PMID:Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT). 1274 May 93

A previous study demonstrated that California ground squirrels (Spermophilus beecheyi) living in the natural environment had, independent of season, a significantly higher mean diurnal body temperature (T(b)) (39.6 degrees C) than either summer (37.5 degrees C) or winter (36.5 degrees C) laboratory maintained animals. Based upon the previous study it has been suggested that California ground squirrels living in the natural environment may have an elevated set-point for body temperature in a manner analogous to a stress fever response. The present study was conducted to determine if season and/or duration of laboratory open-field exposure influenced the magnitude of laboratory open-field stress fever. If stress fever was involved to some extent in the higher body temperature observed in animals from the natural environment, laboratory maintained animals should exhibit a lower magnitude stress fever during the summer months and a higher magnitude stress fever during the winter months. It was hypothesized that laboratory maintained animals would exhibit the same set-point for stress fever T(b) independent of season, and that the duration of open-field exposure would not influence the magnitude of stress fever. Adult California ground squirrels were acclimated to an ambient temperature of 20+/-1.0 degrees C under either LD 14:10 (summer) or LD 10:14 (winter) photoperiod conditions and individuals from both photoperiod conditions were exposed for periods of 2, 4, and 6 h to an open-field arena. An analysis of the data with a two-factor ANOVA demonstrated that season (photoperiod) significantly influenced the magnitude of the stress fever response (1.1+/-0.1 degrees C for summer animals; 2.1+/-0.2 degrees C for winter animals) while there was no significant influence of open-field exposure duration on stress fever magnitude. These results demonstrate that although the set-point for body temperature in unstressed laboratory maintained California ground squirrels varies with season, the set-point for body temperature in open-field stressed animals does not vary with season. These data lend support to the hypothesis that something like stress fever may play some role in the higher body temperature observed in California ground squirrels living in the natural environment.
Comp Biochem Physiol A Mol Integr Physiol 2000 Mar
PMID:Stress fever magnitude in laboratory-maintained California ground squirrels varies with season. 1079 61

Recently, the use of microsatellites as genetic markers has become very popular. While their evolutionary dynamics are not yet fully understood, the emerging picture is that several factors are influencing microsatellite mutation rates. Recent experiments demonstrated a significant effect of repeat motif length on microsatellite mutation rates. Here, we studied the influence of the base composition of the microsatellite. Forty-two microsatellite loci on the second chromosome with the three most abundant dinucleotide repeat motifs (TC/AG, AT/TA, GT/CA) were characterized for six different Drosophila melanogaster populations. Applying ANOVA to the variance in repeat number, we found a significant influence of repeat motif on microsatellite variability. Calculating relative mutation rates, GT/CA appears to have the highest mutation rate, and AT/TA appears to have the lowest. Similar differences in mutation rates were obtained by an alternative method which estimates microsatellite mutation rates from their genomic length distribution.
Mol Biol Evol 2000 Sep
PMID:Microsatellite variability differs between dinucleotide repeat motifs-evidence from Drosophila melanogaster. 1095 44

We previously demonstrated that TSH activates phospholipase D (PLD) in Fischer rat thyroid line (FRTL)-5 cells. To date, two types of mammalian phosphatidylcholine-specific PLD cDNAs, designated as PLD-1 and PLD-2, have been cloned. The present study determined the PLD isoform composition in FRTL-5 thyroid cells and which isoform is regulated by TSH. PLD-1 is activated by small molecular weight G-proteins, such as ADP-ribosylation factor (ARF) and RhoA family members, while PLD-2 is relatively independent of such stimuli. We established the presence of PLD-1 and PLD-2 by Western blot analysis and compared PLD activity in cytosol, membranes and combined fractions in the presence and absence of GTPgammaS. The membrane fraction showed very little activity in the absence of GTPgammaS, but this activity increased approximately 5-fold (P<0.05, ANOVA) in the presence of GTPgammaS. Maximal PLD activity was seen with the combination of membrane plus cytosolic fractions (which contained ARF and RhoA) where the addition of GTPgammaS increased PLD activity approximately 8-fold (P<0.05, ANOVA). To determine the relative activities of PLD-1 and PLD-2 in FRTL-5 thyroid cells, cell-free PLD assays were performed in the presence of GTPgammaS or GDPbetaS with varying concentrations of phosphatidylinositol 4,5-bisphosphate (PIP(2)). PLD-2 contributed only approximately 19% of the total amount of PLD activity in the membranes and PLD-1 was the predominant PLD isoform. TSH stimulated PLD-1 activity by up to 2. 3-fold over control values (P<0.01, ANOVA). To establish the dependence of PLD-1 on small molecular weight G-proteins, the translocations of ARF and RhoA to the membrane fractions was determined after stimulation by TSH. Both ARF and RhoA were maximally translocated to the membrane fraction after 10 min incubation with 100 microU/ml TSH by approximately 1.7- and 2.3-fold over control values, respectively (P<0.02 and P<0.03, ANOVA). It is concluded that TSH stimulates PLD-1 activity in FRTL-5 thyroid cells and this is accompanied by the translocation of ARF and RhoA to the membrane fraction.
Mol Cell Endocrinol 2000 Sep 25
PMID:The characterization of phospholipase D in FRTL-5 thyroid cells. 1100 May 25

There are data to support the notion that adenosine (ADO), a neuromodulator in the CNS, is an important regulator of sleep homeostasis. It has been demonstrated that ADO agonists and antagonists strongly impact upon sleep. In addition, the level of adenosine varies across the sleep/wake cycle and increases following sleep deprivation. Adenosine deaminase (ADA) is a key enzyme involved in the metabolism of ADO. We questioned, therefore, whether there are differences in adenosine deaminase activity in brain regions relevant to sleep regulation. We found that ADA exhibits a characteristic spatial pattern of activity in the rat CNS with the lowest activity in the parietal cortex and highest in the region of the tuberomammillary nucleus (15.0+/-4.8 and 63.4+/-28.0 nmoles/mg protein/15 min, mean+/-S.D., respectively). There were significant differences among the brain regions by one-way ANOVA (F=31.33, df=6, 123, P=0.0001). The regional differences in ADA activity correlate with variations in the level of its mRNA. This suggests that spatial differences in ADA activity are the result of changes in the expression of the ADA gene. We postulate that adenosine deaminase plays an important role in the mechanism that controls regional concentration of adenosine in the brain and thus, it is a part of the sleep-wake regulatory mechanism.
Brain Res Mol Brain Res 2000 Sep 15
PMID:Activity of adenosine deaminase in the sleep regulatory areas of the rat CNS. 1103 59

Apoptosis plays a central role in the cellular remodeling of the developing lung. We determined the spatiotemporal patterns of the cell death regulators Fas and Fas ligand (FasL) during rabbit lung development and correlated their expression with pulmonary and type II cell apoptosis. Fetal rabbit lungs (25-31 days gestation) were assayed for apoptotic activity by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) and DNA size analysis. Fas and FasL expression were analyzed by RT-PCR, immunoblot, and immunohistochemistry. Type II cell apoptosis increased significantly on gestational day 28; the type II cell apoptotic index increased from 0.54 +/- 0.34% on gestational day 27 to 3.34 +/- 1.24% on day 28, P < 0.01 (ANOVA). This corresponded with the transition from the canalicular to the terminal sac stage of development. The day 28 rise in epithelial apoptosis was synchronous with a robust if transient 20-fold increase in FasL mRNA and a threefold increase in FasL protein levels. In contrast, Fas mRNA levels remained constant, suggestive of constitutive expression. Fas and FasL proteins were immunolocalized to alveolar type II cells and bronchiolar Clara cells. The correlation of this highly specific pattern of FasL expression with alveolar epithelial apoptosis and remodeling implicates the Fas/FasL system as a potentially important regulatory pathway in the control of postcanalicular alveolar cytodifferentiation.
Am J Physiol Lung Cell Mol Physiol 2000 Nov
PMID:Fas ligand expression coincides with alveolar cell apoptosis in late-gestation fetal lung development. 1105 34

We report use of an in vitro assay (Barbato et al., 1998: Biol Reprod 58:686-699) to assess binding ability of cauda epididymal mouse sperm to a surrogate zona pellucida and effect of a synthetic peptide (Amann et al., 1999: J Androl 20: 42-46) on fertilization ability in in vitro fertilization (IVF) tests. Sperm from C57Bl/6, CD1, and CF1 mice (4 replicates each) were evaluated for binding ability after exposure to 0 (control) and 80-1280 pM peptide. For control sperm, endogenous binding was C57Bl/6 < CD1 = CF1 (P < 0.05, 1-way ANOVA). Across all three strains, exposure to > 320 pM peptide increased relative binding of sperm (P < 0.05; 2-way general linear model; GLM). Strains differed both in basal binding ability and in response to synthetic peptide. To determine if IVF rate increased after exposure of sperm to peptide, ova from B6C3 mice (four replicate pools) were collected after eCG and hCG stimulation. Cumulus-oocyte complexes (COC; 8-15 ova in each of 3-6 drops/treatment) were incubated with hyperactivated C57Bl/6 sperm at approximately 1500 sperm per ovum. Data for incubations were corrected for false-positive classification to yield a better estimate of true cleavage rate, and then related to results observed with a tenfold greater sperm concentration. Relative cleavage rates were 0 peptide (0.48); 420 pM (0.78, P < 0.05); and 840 pM (0.90, P < 0.01; GLM and Tukey tests). IVF rate was increased by exposure of mouse sperm to peptide at concentrations effective in the in vitro assay, and use of peptide allowed use of 1/10 as many sperm.
Mol Reprod Dev 2000 Dec
PMID:Increased in vitro binding and fertilizing ability of mouse sperm exposed to a synthetic peptide. 1106 70

Accumulation of neurobiological knowledge points to neurodevelopmental origins for certain psychotic and mood disorders. Recent landmark postmortem reports implicate Reelin, a secretory glycoprotein responsible for normal lamination of brain, in the pathology of schizophrenia and bipolar disorders. We employed quantitative immunocytochemistry to measure levels of Reelin protein in various compartments of hippocampal formation in subjects diagnosed with schizophrenia, bipolar disorder and major depression compared to normal controls. Significant reductions were observed in Reelin-positive adjusted cell densities in the dentate molecular layer (ANOVA, P < 0.001), CA4 area (ANOVA, P < 0.001), total hippocampal area (ANOVA, P < 0.038) and in Reelin-positive cell counts in CA4 (ANOVA, P < 0.042) of schizophrenics vs controls. Adjusted Reelin-positive cell densities were also reduced in CA4 areas of subjects with bipolar disorder (ANOVA, P < 0.001) and nonsignificantly in those with major depression. CA4 areas were also significantly reduced in schizophrenic (ANOVA, P < 0.009) patients. No significant effects of confounding variables were found. The exception was that family history of psychiatric illness correlated strongly with Reelin reductions in several areas of hippocampus (CA4, adjusted cell density, F = 13.77, P = 0.001). We present new immunocytochemical evidence showing reductions in Reelin expression in hippocampus of subjects with schizophrenia, bipolar disorder and major depression and confirm recent reports documenting a similar deficit involving Reelin expression in brains of subjects with schizophrenia and bipolar disorder.
Mol Psychiatry 2000 Nov
PMID:Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. 1112 96

Throughout the world, the highly selfing annual common groundsel, Senecio vulgaris (Asteraceae) is a common weed. Recently, it has also colonized ecological compensation areas in agro-ecosystems. We investigated the genetic structure of S. vulgaris using random amplified polymorphic DNA (RAPD) profiles of 80 plants from nine populations representing three habitat types in two regions in Switzerland. RAPD variation among regions (19.8%), among populations within regions (19.2%) and within populations (61.1%) was highly significant (ANOVA; P < 0.001). Gene flow estimated from the observed differentiation among populations (PhiST = 0.382) was low (assuming Wright's island model, Nem = 0.404). Genetic distances between pairs of populations were significantly correlated with geographical distances (Mantel test; r = 0.37, P < 0.03). Molecular variance obtained with AMOVA was lowest in the small populations in compensation areas (1.13), intermediate in vineyard populations (2.49), all located in northern Switzerland and highest in the larger vegetable field populations from western Switzerland (3.41; P < 0.05). Overall, there was a positive correlation of molecular variance and population size (P < 0.05), as expected under genetic drift. However, molecular variance was negatively correlated with population size among populations in ecological compensation areas, suggesting that selection was also important. We also applied triazine herbicide to leaves of three offspring of each of the 80 plants. Plants from populations of compensation areas showed higher mean levels and reduced variation in the resistance to triazine herbicide than plants from vineyards and vegetable fields. This suggests that compensation areas were colonized from adjacent corn fields, in which there has been selection for herbicide resistance. We discuss the implications of our results for the biological control of S. vulgaris.
Mol Ecol 2001 Jan
PMID:Genetic structure of the annual weed Senecio vulgaris in relation to habitat type and population size. 1125 83


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